Pregnancy Outcomes in Association with STDs including genital HSV-2 shedding in a South African Cohort Study.

OBJECTIVES: Genital herpes simplex virus-2 (HSV-2) shedding in pregnant women in association with neonatal herpes infection has been widely studied but there is limited evidence of its association with pregnancy outcomes. METHODS: In this retrospective observational study, we included a subgroup of pregnant women who were enrolled in a randomized control behavioural intervention study that was conducted in South Africa in 2008-2010. In pregnancy, women had a HIV rapid test done and a genital swab taken to test for curable STIs and HSV-2 DNA. Subsequent visits were scheduled for 6, 10, 14 weeks and 9 months post-delivery. Pregnancy outcomes were documented at the 6-week or 10-week postpartum visit. Women were treated syndromically for curable STIs. RESULTS: Among 615 women included in this data analysis, 36.6% (n=225) tested HIV positive and 8.3% (n=51) tested positive for genital HSV-2 shedding during pregnancy. Women <24 years and HIV-1 seropositive women were 1.5 and 2.5 times more likely to test positive for HSV-2 genital shedding respectively. STI treatment records were available for 158/205 (77.1%) women; all 87 women with symptomatic STIs were treated the same day, and 50/71 (70.4%) asymptomatic women received treatment at the subsequent visit. Remaining 21 (29.6%) asymptomatic women did not receive treatment because they failed to return for antenatal follow-up. In a multivariable regression analysis, genital HSV-2 shedding, HIV-1, Neisseria gonorrhoea, Chlamydia trachomatis and Trichomanas vaginalis were not associated with preterm deliveries, still births and low birth weight. However with stratification by treatment for a STI, asymptomatic women who were not treated were 3.3 times more likely to deliver prematurely (33.3%; n=6/18) when compared to women who were treated during pregnancy (13.2%; n=15/114) (p=0.042). CONCLUSIONS: Genital HSV-2 shedding in pregnancy does not appear to alter pregnancy outcomes. Untreated curable STIs (T.vaginalis, C.trachomatis, N.gonorrhoea) were more likely associated with preterm births.

Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: HPTN 046 compared the efficacy and safety of infant nevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to t NVP or placebo to prevent postnatal infection: we report final 18-month outcomes. METHODS: Randomized, placebo-controlled trial in 4 African countries. Infant diagnostic HIV testing was performed regularly from birth through 18 months. Kaplan-Meier analysis was used to assess 18-month cumulative infant HIV infection, HIV infection/or death, and mortality rates. RESULTS: Between 6 weeks and 6 months, postnatal HIV infection rates were significantly lower among infants receiving daily NVP from 6 weeks to 6 months 1.1% [95% confidence interval (CI): 0.2% to 1.8%], compared with placebo 2.4% (95% CI: 1.3% to 2.6%), P = 0.049, but not significantly lower thereafter. Eighteen-month postnatal infection rates were low: 2.2% (95% CI: 1.1% to 3.3%) versus 3.1% (95% CI: 1.9% to 4.4%), respectively, P = 0.28. Mortality and HIV infection/death did not differ between arms at any age. Infants of women receiving antiretroviral therapy (ART) for their own health had the lowest 18-month postnatal infection rates (0.5%, 95% CI: 0.0% to 1.1%). However, HIV infection/death rates at 18 months were not significantly different for infants of mothers on ART (3.7%, 95% CI: 1.9% to 5.5%), and infants of mothers with CD4 counts of ≥ 350 cells per cubic millimeter not receiving ART (4.8%, 95% CI: 2.7% to 6.8%; P = 0.46). There were no differences in adverse events between study arms. CONCLUSIONS: This trial demonstrated early but not late differences in postnatal HIV transmission among infants randomized at age 6 weeks to extended NVP or placebo, underscoring the importance of continued prophylaxis throughout breastfeeding.

Evaluation of a 4th generation rapid HIV test for earlier and reliable detection of HIV infection in pregnancy.

BACKGROUND: Currently used 3rd generation rapid HIV-tests in resource-limited settings do not detect acute HIV-infections (AHI). They are known to detect HIV-infections after or late in the "window period". Detecting incident-HIV infections early in pregnancy increases opportunities for initiating antiretroviral prophylaxis to prevent mother-to-child transmission of HIV. OBJECTIVES: We evaluated the Determine(®) HIV1/2 Ag/Ab Combo Rapid Test (Combo RT), a 4th generation test against two 3rd generation tests (SENSA-HIV1/2/0 Tri-line, SD-Bioline) for early detection of HIV-infection in pregnancy. STUDY DESIGN: In a cohort study, plasma samples from 32 pregnant women who seroconverted at a subsequent antenatal visit (incident-infection), samples from 189 women who tested HIV positive at baseline (established-infections) and samples from 32 women remaining HIV-seronegative at a subsequent antenatal visit were tested with 3rd generation (antibody detection only) and 4th generation (antibody/antigen detection) rapid HIV tests. The HIV-1 NucliSENSEasyQ(®) v2.0 PCR test was used to quantify HIV-viral copies in women with incident HIV-infections. RESULTS: Eighteen of 32 (56.3%) women (incident-infections) had detectable viral copies (baseline); 16 (88.9%) were antibody reactive with the Combo RT. None of the 32 specimens were reactive on the antigen component of the Combo RT. The sensitivity and specificity of the Combo RT in detecting HIV infections prior to seroconversion is 59.4% (95%CI 40.6-76.3) and 96.9% (95%CI 83.8-99.9) respectively. The Combo RT detected 94.0% of all HIV-infections if used as a screening test (baseline) compared to 85.5% detected by 3rd generation tests. CONCLUSIONS: The Combo RT does not identify AHI but is superior to 3rd generation tests in detecting HIV antibody responses.

Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months. METHODS: In our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412. FINDINGS: Between June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1·1% (95% CI 0·3-1·8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2·4% (1·3-3·6) of controls (difference 1·3%, 95% CI 0-2·6), equating to a 54% reduction in transmission (p=0·049). However, mortality (1·2% for nevirapine vs 1·1% for placebo; p=0·81) and combined HIV infection and mortality rates (2·3%vs 3·2%; p=0·27) did not differ between groups at 6 months. 125 (16%) of 758 infants given extended nevirapine and 116 (15%) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups. INTERPRETATION: Nevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age. FUNDING: US National Institutes of Health.

High HIV incidence during pregnancy: compelling reason for repeat HIV testing.

OBJECTIVE: To determine the incidence of HIV during pregnancy as defined by seroconversion using a repeat HIV rapid testing strategy during late pregnancy. DESIGN: Cross-sectional study nested in a prevention of mother-to-child transmission program METHODS: Pregnant women were retested between 36 and 40 weeks of gestation, provided that they had been tested HIV negative at least 3 months prior. RESULTS: Among the 2377 HIV-negative women retested, 1099 (46.2%) and 1278 (53.4%) were tested at urban and rural health facilities, respectively. Seventy-two women (3%) were HIV-positive (679 woman years of exposure) yielding a HIV incidence rate of 10.7/100 woman years [95% confidence interval (CI) 8.2-13.1]. HIV incidence in pregnancy was higher but not statistically significant at the urban facilities (12.4/100 woman years versus 9.1/100 woman years) and at least two-fold higher among the 25-29 and 30-34-year age groups (3.8 and 4.5%, respectively) as compared with the less than 20-year age group (1.9%). Single women were at 2.5 times higher risk of seroconverting during pregnancy (P = 0.017). CONCLUSION: HIV incidence during pregnancy is four times higher than in the nonpregnant population reported in a recent survey. Public health programs need to continue to reinforce prevention strategies and HIV retesting during pregnancy. The latter also offers an additional opportunity to prevent mother-to-child transmission and further horizontal transmission. Further research is required to understand the cause of primary HIV infection in pregnancy.